Field of the Invention
This invention relates to systems and methods for managing process conditions in a container or chamber, including controlling bioreactors for cell cultures and microbial fermentation, semiconductor fabrication and liquid chromatography.
Description of the Related Art
Many manufacturing and biological generation processes consist of a complex sequence of steps and require positive control over environmental conditions to consistently reproduce a desired result. In cell culture growth, for example, geneticists manipulate DNA by identifying, excise, move and place genes into a variety of cells that are genetically quite different from the source cell, and these recombinant cells can produce proteins that may be of immense commercial value. Once the gene is successfully transferred to another cell, the growth process for the cell must be closely monitored and controlled to provide an effective environment that promotes cell viability. Understanding and documenting environmental conditions affecting the viability of cells, and accurately controlling such conditions allows consistent reproduction of the cell culture process.
Cell culture processes are commonly developed and optimized in a benchtop scaled bioreactor, and then be scaled-up to a large production process according to commercial demands. The process may take weeks or even months, and include numerous changes to the conditions of the media, or solution, contained in the bioreactor during this period. For example, desired conditional changes to the solution can include adjustments to pH, temperature, and dissolved oxygen. Providing precise amounts of certain fluids or gasses to the bioreactor, either directly or indirectly (e.g., using fluids to heat or cool a solution) changes these and other conditions of the solution. Typically, monitoring a process is accomplished by entering data from a bioreactor sensor into a logbook, from time-to-time. Agitating the solution, or adding fluids or gasses to the solution, is also generally done manually in an amount estimated by the attending operator, and recorded in a paper logbook. Poor documentation and/or imprecisely adding fluid or gas to the process can result in an unacceptably high level of uncertainty as to the steps required for the process, thereby making a faithful reproduction of the process nearly impossible.
Additionally, government regulation of certain manufacturing processes may require implementation of strict documentation and control procedures. For example, the Food and Drug Administration's (FDA's) 21 Code of Federal Regulations Part 11 applies to records in electronic form that are created, modified, maintained, archived, retrieved, or transmitted under any records requirement set forth in Agency regulations, and to electronic records submitted to the Agency under the Federal Food, Drug, and Cosmetic Act and the Public Health Service Act. Part 11 includes provisions related to limiting system access to authorized individuals, use of operational checks, use of authority checks, and use of electronic signatures. As biological control systems move towards electronic implementations, it is advantageous to design systems to easily incorporate regulations governing electronic records and control procedures.